TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18085	54478;54479;54480	chr2:178604836;178604835;178604834	chr2:179469563;179469562;179469561
N2AB	16444	49555;49556;49557	chr2:178604836;178604835;178604834	chr2:179469563;179469562;179469561
N2A	15517	46774;46775;46776	chr2:178604836;178604835;178604834	chr2:179469563;179469562;179469561
N2B	9020	27283;27284;27285	chr2:178604836;178604835;178604834	chr2:179469563;179469562;179469561
Novex-1	9145	27658;27659;27660	chr2:178604836;178604835;178604834	chr2:179469563;179469562;179469561
Novex-2	9212	27859;27860;27861	chr2:178604836;178604835;178604834	chr2:179469563;179469562;179469561
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-19
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.168
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/A	rs1274377339	-1.259	0.101	N	0.32	0.147	0.311691414656	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
T/A	rs1274377339	-1.259	0.101	N	0.32	0.147	0.311691414656	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
T/A	rs1274377339	-1.259	0.101	N	0.32	0.147	0.311691414656	gnomAD-4.0.0	2.03046E-06	None	None	None	None	N	None	3.49724E-05	0	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.1071	likely_benign	0.1132	benign	-0.963	Destabilizing	0.101	N	0.32	neutral	N	0.49972247	None	None	N
T/C	0.4171	ambiguous	0.4481	ambiguous	-0.625	Destabilizing	0.983	D	0.516	neutral	None	None	None	None	N
T/D	0.5765	likely_pathogenic	0.6182	pathogenic	-1.112	Destabilizing	0.264	N	0.404	neutral	None	None	None	None	N
T/E	0.4126	ambiguous	0.4633	ambiguous	-0.929	Destabilizing	0.129	N	0.367	neutral	None	None	None	None	N
T/F	0.2121	likely_benign	0.2491	benign	-0.61	Destabilizing	0.716	D	0.503	neutral	None	None	None	None	N
T/G	0.334	likely_benign	0.3476	ambiguous	-1.382	Destabilizing	0.228	N	0.376	neutral	None	None	None	None	N
T/H	0.2395	likely_benign	0.2686	benign	-1.526	Destabilizing	0.005	N	0.444	neutral	None	None	None	None	N
T/I	0.1402	likely_benign	0.1793	benign	0.126	Stabilizing	0.002	N	0.392	neutral	N	0.480411367	None	None	N
T/K	0.2791	likely_benign	0.3294	benign	-0.496	Destabilizing	0.002	N	0.333	neutral	N	0.472709227	None	None	N
T/L	0.0856	likely_benign	0.0997	benign	0.126	Stabilizing	0.129	N	0.379	neutral	None	None	None	None	N
T/M	0.086	likely_benign	0.0951	benign	0.081	Stabilizing	0.716	D	0.523	neutral	None	None	None	None	N
T/N	0.1507	likely_benign	0.1659	benign	-1.101	Destabilizing	0.01	N	0.211	neutral	None	None	None	None	N
T/P	0.7337	likely_pathogenic	0.7458	pathogenic	-0.204	Destabilizing	0.523	D	0.546	neutral	N	0.506909412	None	None	N
T/Q	0.2312	likely_benign	0.2586	benign	-0.882	Destabilizing	0.264	N	0.515	neutral	None	None	None	None	N
T/R	0.2338	likely_benign	0.2732	benign	-0.689	Destabilizing	0.007	N	0.38	neutral	N	0.491852348	None	None	N
T/S	0.1151	likely_benign	0.1212	benign	-1.336	Destabilizing	0.021	N	0.2	neutral	N	0.432473183	None	None	N
T/V	0.1245	likely_benign	0.1484	benign	-0.204	Destabilizing	0.129	N	0.299	neutral	None	None	None	None	N
T/W	0.5842	likely_pathogenic	0.6313	pathogenic	-0.77	Destabilizing	0.983	D	0.555	neutral	None	None	None	None	N
T/Y	0.2861	likely_benign	0.3134	benign	-0.384	Destabilizing	0.716	D	0.525	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.